Sodium diacetate is a crystalline powder particle consisting of acetic acid and sodium acetate at the molar ratio of 1:1. In the field of foods, it is used as a food additive, such as an acidic ingredient (powdery acetic acid and Sushi Seasoning Mixes) or a pH adjuster, or a fungicide or a sequestering agent, or an adhesion preventing agent. In addition, in solid dialysis preparations for patients with renal failure, sodium diacetate is known to be incorporated for preventing the volatilization of a pH adjuster, acetic acid (Patent Literatures 1 to 3).
Sodium diacetate is mainly prepared by mixing of acetic acid and sodium carobnate or hydroxide (Non-patent Literature 1). Further, sodium diacetate may be prepared by spraying a mist of brewed vinegar to sodium acetate (Patent Literature 4).
The commercially available conventional sodium diacetates prepared as described above have smaller crystal size and lower stability to air and heat, and thus acetic acid is easily vaporized, leading to the generation of an acetic acid odor. Therefore, when it is used in dialysates, there is a problem that the an acetic acid odor is generated by the variation of pH, or by dissolving the dialysates in the manufacturing processes or in the medical settings, resulting in an obstacle for handling it.
On the other hand, in the field of foods, technologies for reducing the acetic acid odor by adding an agent such as maltitol, erythritol, and betaine for masking the odor have been proposed (Patent Literatures 5 and 6, etc.). However, such technologies were inappropriate for dialysates which are medicaments, because a huge amount of such additives is necessary for masking the odor.
Further, it has been suggested to aspirate the odor after the addition of acetic acid to granules during the preparation of dialysis preparations (Patent Literatures 7 and 8). However, it was not possible to suppress the volatilization of acetic acid with aging after the aspiration.
In dialysates, sodium bicarbonate is included to correct the acid-base balance of renal failure patients. In order to avoid a reaction of sodium bicarbonate with any other electrolyte components, the dialysates are generally prepared separately as an A agent (a formulation comprising calcium chloride and magnesium chloride, and so on without sodium bicarbonate) and a B agent (sodium bicarbonate), and they are mixed before use in order to use as dialysates. Previously, a liquid type agent was used as an A agent. Because of the massiveness and the inconvenient handling of the liquid, a solid dialysis preparation, which was solidified (powdered), has become prevalent. A known method for preparing an A agent for the solid dialysis preparation comprises using a suspension of potassium chloride, magnesium chloride and sodium acetate as a binder (binding agent) (Patent Literature 9). However, it was not possible to prepare an A agent exhibiting sufficient content uniformity by said method.
In addition, acetic acid at 8 to 12 mEq/L is predominantly used as a pH adjuster in a conventional dialysate, while said value is 80- to 120-times higher than the reference value in vivo. Since there is also an report that an increase of the blood concentration of acetic acid causes a significant allergic reaction (acetate intolerance) (Non-patent Literature 2), a dialysate with lower acetic acid concentration closer to a reference value, such as an acetic acid concentration below 5 mEq/L is needed. As for such dialysates, the low-acetate dialysates in which total acetate ion is not less than 2 mEq/L and less than 6 mEq/L have been developed (Patent Literatures 10 to 12).
Further, in case of the solid dialysis preparations using acetic acid, there is a report that the acetic acid odor is not generated when the molar ratio of acetic acid to sodium acetate in the formulations is from 1:3.6 to 4.3, while a strong acetic acid odor is generated if the ratio deviates from the range. (Patent Literature 13). However, when preparing a solid dialysis preparation with a low-acetate concentration, the pH is increased by adding the components in the amount covered by said ratio, and fine particles of calcium carbonate will occur when mixing with B agent. On the other hand, when preparing an A agent within the pH range which does not generate the fine particles, a strong acetic acid odor occurs, because the ratio of acetic acid to sodium acetate is 1:1, namely, beyond the above described range of the ratio.